Grant: Operating Grant

. Little is known of the clinical significance and the mechanisms starting and ending inflammation. Periodontal diseases are the 2nd most common infectious diseases in humans costing Canadians >$2 billion/year to treat. A lack of diagnostic tests impedes early accurate diagnosis resulting in an inability to provide the best and early treatment. Other common chronic inflammatory diseases such as tendonitis, fibrosis and arthritis are also difficult to accurately diagnose. In inflammation the tissue proteins are dissolved by enzymes termed "proteases" causing loose teeth in gum disease, painful tendon attachments in tendonitis, and swollen sore joints in arthritis. Tissue and blood cells that fight infection make important proteases called "MMPs". MMPs dissolve critical components that add strength to tissues, joints and tendons, and hold teeth in place. However, some MMPs orchestrate the body's resistance to infection, improving healing and so are beneficial. To understand gum disease we first identified proteases and the proteins they dissolve in inflammation of mouse skin as a test case. We call this overall picture of inflammation a "proteolytic signature". We suggest that the dissolved protein stubs of the signature can also be important tell tale signs of inflammation called "biomarkers". With our new techniques we are ready to study inflammation in humans. First we will study oral inflammation using tissues that are typically discarded during wisdom tooth extraction as a reliable source of normal and acutely inflamed human tissue. This will form baseline studies for the more serious chronic periodontitis. Our biomarker proteins can also be used as a new clinical test for gum disease and to assess treatment options. Moreover, select biomarkers will point to new drug targets to treat gum disease to improve the dental health of Canadians and reduce health costs. The biomarkers and drug targets we find may be useful in other chronic inflammatory diseases.